This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: Depression is a widely diagnosed and highly debilitating disorder. Cognitive theories of depression posit that depressed individuals are characterized by cognitive biases favoring in the processing of negative affective information. An information-processing bias frequently associated with major depression is increased memory sensitivity for negative information and, often, decreased memory sensitivity for positive material. Importantly, the amygdala has been centrally implicated in encoding and memory for emotionally valenced material and has been found to show elevated resting state activity in depression. The primary goal of this study is to assess the role of amygdalar activation in the negative memory bias associated with depression. Methods and Results: Ten participants meeting criteria for major depressive disorder in the absence of other Axis-I disorders and ten age and sex-matched healthy control participants served as participants in this study. Functional magnetic resonance imaging (fMRI) was used to measure neural activation during presentation and affective evaluation of positive, neutral and negative pictures. One week following scanning, participants engaged in an out-of-scanner recognition memory task during which they were presented with pictures that they saw in the scanner and with never- seen pictures, and were asked to rate the familiarity of each picture. Memory sensitivity for negative pictures was significantly higher in depressed than in control participants;the two groups of participants did not differ in memory sensitivity for positive pictures. Corresponding to this finding, activity in the left amygdala was significantly higher during encoding of subsequently remembered negative pictures in depressed than in control participants, but not during encoding of neutral or positive pictures. To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)